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Comparison of bone and renal effects in HIV-infected adults switching to abacavir or tenofovir based therapy in a randomized trial.

ABSTRACT: Our objective was to compare the bone and renal effects among HIV-infected patients randomized to abacavir or tenofovir-based combination anti-retroviral therapy.In an open-label randomized trial, HIV-infected patients were randomized to switch from zidovudine/lamivudine (AZT/3TC) to abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC). We measured bone mass density (BMD) and bone turnover biomarkers (osteocalcin, osteocalcin, procollagen type 1 N-terminal propeptide (P1NP), alkaline phosphatase, type I collagen cross-linked C-telopeptide (CTx), and osteoprotegerin). We assessed renal function by estimated creatinine clearance, plasma cystatin C, and urinary levels of creatinine, albumin, cystatin C, and neutrophil gelatinase-associated lipocalin (NGAL). The changes from baseline in BMD and renal and bone biomarkers were compared across study arms.Of 40 included patients, 35 completed 48 weeks of randomized therapy and follow up. BMD was measured in 33, 26, and 27 patients at baseline, week 24, and week 48, respectively. In TDF/FTC-treated patients we observed significant reductions from baseline in hip and lumbar spine BMD at week 24 (-1.8% and -2.5%) and week 48 (-2.1% and -2.1%), whereas BMD was stable in patients in the ABC/3TC arm. The changes from baseline in BMD were significantly different between study arms. All bone turnover biomarkers except osteoprotegerin increased in the TDF/FTC arm compared with the ABC/3TC arm, but early changes did not predict subsequent loss of BMD. Renal function parameters were similar between study arms although a small increase in NGAL was detected among TDF-treated patients.Switching to TDF/FTC-based therapy led to decreases in BMD and increases in bone turnover markers compared with ABC/3TC-based treatment. No major difference in renal function was observed.Clinicaltrials.gov NCT00647244.

SUBMITTER: Rasmussen TA

PROVIDER: S-EPMC3315554 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Comparison of bone and renal effects in HIV-infected adults switching to abacavir or tenofovir based therapy in a randomized trial.

Rasmussen Thomas A TA Jensen Danny D Tolstrup Martin M Nielsen Ulla S US Erlandsen Erland J EJ Birn Henrik H Østergaard Lars L Langdahl Bente L BL Laursen Alex L AL

PloS one 20120329 3

<h4>Introduction</h4>Our objective was to compare the bone and renal effects among HIV-infected patients randomized to abacavir or tenofovir-based combination anti-retroviral therapy.<h4>Methods</h4>In an open-label randomized trial, HIV-infected patients were randomized to switch from zidovudine/lamivudine (AZT/3TC) to abacavir/lamivudine (ABC/3TC) or tenofovir/emtricitabine (TDF/FTC). We measured bone mass density (BMD) and bone turnover biomarkers (osteocalcin, osteocalcin, procollagen type 1 ...[more]

PMID: 22479327

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Project description:Therapy with tenofovir is associated with lower bone mineral density (BMD), higher markers of bone turnover and increased fracture risk in HIV-infected adults. Bone structural parameters generated by hip structural analysis may represent a separate measure of bone strength, but have not been assessed in HIV.Dual-energy X-ray absorptiometry (DXA) scans from 254 HIV-infected adults randomised to simplify their existing dual nucleoside analogue reverse transcriptase inhibitor therapy to coformulated tenofovir-emtricitabine or abacavir-lamivudine were analysed using DXA-derived hip structural analysis software. Hip structural parameters included femoral strength index, section modulus, cross-sectional area, and cross-sectional moment of inertia. We used one-way ANOVA to test the relationship between nucleoside analogue type at baseline and structural parameters, multivariable analysis to assess baseline covariates associated with femoral strength index, and t-tests to compare mean change in structural parameters over 96 weeks between randomised groups.Participants taking tenofovir at baseline had lower section modulus (-107.3 mm2, p?=?0.001), lower cross-sectional area (-15.01 mm3, p?=?0.001), and lower cross-sectional moment of inertia (-2,036.8 mm4, p?=?0.007) than those receiving other nucleoside analogues. After adjustment for baseline risk factors, the association remained significant for section modulus (p?=?0.008) and cross-sectional area (p?=?0.002). Baseline covariates significantly associated with higher femoral strength index were higher spine T-score (p?=?0.001), lower body fat mass (p<0.001), lower bone alkaline phosphatase (p?=?0.025), and higher osteoprotegerin (p?=?0.024). Hip structural parameters did not change significantly over 96 weeks and none was significantly affected by treatment simplification to tenofovir-emtricitabine or abacavir-lamivudine.In this population, tenofovir use was associated with reduced composite indices of bone strength as measured by hip structural analysis, but none of the structural parameters improved significantly over 96 weeks with tenofovir cessation.ClinicalTrials.gov NCT00192634.

Project description:The use of fixed-dose combination nucleoside reverse-transcriptase inhibitors (NRTIs) with a nonnucleoside reverse-transcriptase inhibitor or a ritonavir-boosted protease inhibitor is recommended as initial therapy in patients with human immunodeficiency virus type 1 (HIV-1) infection, but which NRTI combination has greater efficacy and safety is not known.In a randomized, blinded equivalence study involving 1858 eligible patients, we compared four once-daily antiretroviral regimens as initial therapy for HIV-1 infection: abacavir-lamivudine or tenofovir disoproxil fumarate (DF)-emtricitabine plus efavirenz or ritonavir-boosted atazanavir. The primary efficacy end point was the time from randomization to virologic failure (defined as a confirmed HIV-1 RNA level > or = 1000 copies per milliliter at or after 16 weeks and before 24 weeks, or > or = 200 copies per milliliter at or after 24 weeks).A scheduled interim review by an independent data and safety monitoring board showed significant differences in virologic efficacy, according to the NRTI combination, among patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more. At a median follow-up of 60 weeks, among the 797 patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more, the time to virologic failure was significantly shorter in the abacavir-lamivudine group than in the tenofovir DF-emtricitabine group (hazard ratio, 2.33; 95% confidence interval, 1.46 to 3.72; P<0.001), with 57 virologic failures (14%) in the abacavir-lamivudine group versus 26 (7%) in the tenofovir DF-emtricitabine group. The time to the first adverse event was also shorter in the abacavir-lamivudine group (P<0.001). There was no significant difference between the study groups in the change from the baseline CD4 cell count at week 48.In patients with screening HIV-1 RNA levels of 100,000 copies per milliliter or more, the times to virologic failure and the first adverse event were both significantly shorter in patients randomly assigned to abacavir-lamivudine than in those assigned to tenofovir DF-emtricitabine. (ClinicalTrials.gov number, NCT00118898.)

Dataset Information

Comparison of bone and renal effects in HIV-infected adults switching to abacavir or tenofovir based therapy in a randomized trial.

Publications

Comparison of bone and renal effects in HIV-infected adults switching to abacavir or tenofovir based therapy in a randomized trial.

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